Linking genes to addiction

Investigators have long known that genetic inheritance makes a contribution both to the likelihood that someone who takes cocaine, heroin, other opiate drugs and tobacco will become addicted and to whether a person will try the drug in the first place. Recent advances in genomics have made it possible to begin to track down the genes responsible for the increased risk of addiction. From there, scientists hope to be better positioned to develop new and more effective treatments for drug abuse. Two recent, separate grants to Yale totaling $9 million from the National Institute of Drug Abuse (NIDA) are supporting the first-ever large-scale, multi-center study to identify those genes.

NIDA gave Yale $6 million to study cocaine dependence in 1999 and then an additional $3 million last August to study opioid addictions. Tobacco addiction will also be studied because of the high frequency with which it can occur with abuse of the other drugs. According to the studies’ principal investigator, Joel E. Gelernter, M.D., associate professor of psychiatry, the project represents a landmark opportunity to find the genetic basis for the addictions. “The fact,” he said, “that the genetic contribution [to drug addiction] is so high means that the odds of us finding something in terms of specific genes are very good.”

To make such a finding, however, requires recruitment of some 750 families at several different sites around the country. The goal is to recruit addicted sibling pairs and type markers throughout the entire genome. This will give the investigators a good chance to identify the more important genes that influence risk for drug dependence.

Eventually, the study should result in a better understanding of the physiological basis of addiction. “The fantasy,” said Gelernter, “would be that we could do a simple DNA test of someone whom we thought was at risk early on, and then do some type of modification of the environment that might be protective. Or we could put the person on some type of medication before he or she was ever exposed to cocaine to modify what the risk would be.” One such medication based on the work of Yale scientists, a vaccine that can prevent cocaine from getting the user high, is currently being studied in clinical trials.